Arbour N, Talbot P J
Laboratory of Neuroimmunovirology, Institut Armand-Frappier, Université du Québec, Laval, Canada.
Adv Exp Med Biol. 1998;440:575-81. doi: 10.1007/978-1-4615-5331-1_75.
Human coronaviruses (HCV) have been associated mainly with infections of the respiratory tract. Accumulating evidence from in vitro and in vivo observations is consistent with the neurotropism of these viruses in humans. To verify the possibility of a persistent infection within the central nervous system (CNS), various human cell lines of neural origin were tested for their ability to maintain chronic infection by both known strains of HCV, OC43 and 229E. Production of infectious progeny virions was monitored by an immunoperoxydase assay on a susceptible cell line and viral RNA was observed after RT-PCR. Astrocytic cell lines U-373 MG and U-87 MG did not sustain a persistent HCV-229E infection, even though they were susceptible to an acute infection by this virus. On the other hand, these two cell lines could maintain a persistent infection by HCV-OC43 for as many as 25 cell passages (about 130 days of culture). Relatively stable titers of infectious viral particles, as well as apparently constant amounts of viral RNA were detected throughout the persistent infection of U-87 MG cells. However, persistent infection of U-373 MG cells was accompanied by the detection of infectious viral particles from passage 0 to passage 13 and then from passage 20 to the end of the experiment. This gap in the production of infectious virions was correlated by a drop in the apparent amount of viral RNA detected at passages 15 and 20. These results confirm the ability of HCV-OC43 to persistently infect cells of an astrocytic lineage and, together with our previous observations of HCV infection of primary cultures of human astrocytes and the detection of HCV RNA in human brains, are consistent with the possibility that this human coronavirus could persist in the human CNS by targeting astrocytes.
人类冠状病毒（HCV）主要与呼吸道感染相关。来自体外和体内观察的越来越多的证据与这些病毒在人类中的嗜神经性一致。为了验证中枢神经系统（CNS）内持续感染的可能性，测试了各种神经源性人类细胞系维持已知HCV毒株OC43和229E慢性感染的能力。通过对易感细胞系进行免疫过氧化物酶测定监测感染性子代病毒颗粒的产生，并在逆转录聚合酶链反应（RT-PCR）后观察病毒RNA。星形胶质细胞系U-373 MG和U-87 MG不能维持HCV-229E的持续感染，尽管它们易受该病毒的急性感染。另一方面，这两种细胞系可以维持HCV-OC43的持续感染多达25代细胞传代（约130天培养）。在U-87 MG细胞的整个持续感染过程中检测到相对稳定的感染性病毒颗粒滴度以及明显恒定的病毒RNA量。然而，U-373 MG细胞的持续感染伴随着从第0代到第13代以及然后从第20代到实验结束时感染性病毒颗粒的检测。感染性病毒颗粒产生的这种差距与在第15代和第20代检测到的病毒RNA表观量下降相关。这些结果证实了HCV-OC43持续感染星形胶质细胞系细胞的能力，并且与我们先前对人类星形胶质细胞原代培养物的HCV感染观察以及在人类大脑中检测到HCV RNA一起，与这种人类冠状病毒可能通过靶向星形胶质细胞在人类CNS中持续存在的可能性一致。
